Several reports have appeared concerning the accelerated lipolysis which occurs in adipose tissue of experimental animals and humans with cancer. The general mechanism has been shown to be due to increased fatty acid mobilization rather than to decreased lipogenesis. The precise mechanism underlying this tumor-induced lipolysis, however, remains to be determined. Several hormones, which are both lipolytic and anti-lipolytic in nature, are known to exist. Preliminary studies have shown that hypophysectomy decreases tumor-induced lipolysis, and that adipose tissue from animals bearing the experimenta tumor intramuscularly is more sensitive to the lipolytic action of norepinephrine. In addition, tumor-bearing animals exhibit increased levels of plasma adrenocorticotropic hormone. In addition, circulating levels of the anti-lipolytic hormone insulin were decreased in as few as three days following intramuscular inoculation with tumor. The objectives of the proposed project are to study the effects which the Walker 256 experimental cacinoma might have on the circulating levels of the various lipolytic hormones. The effect of tumor on insulin levels will be studied further. These hormones will be determined in serum from rats bearing the tumor intramuscularly at various stages of tumor growth by radioimmunoassay or, in the case of corticosterone, by fluorometry. A second series of experiments will be run to determine if serum from tumor-bearing animals contains elevated levels of a lipolytic hormone not quantifiable by currently available techniques. In these studies adipose tissue from normal rats will be incubated with varying concentrations of serum from normal or tumor-bearing rats for varying lengths of time (up to 3 hours) and determining medium free fatty acid levels. Finally, the production of lipolytic substance by the tumor itself will be evaluated by culturing the tumor cells in vitro and sampling the culture medium for lipolytic factors. Also, where practical, endocrine organs will be incubated with varying concentrations of cell-free culture medium to deterine if the tumor produces a substance which stimulates the secretion of lipolytic hormones by these organs. When not practical, culture medium will be injected in vivo and the blood serum assayed for increased lipolytic hormones.